Method for Manufacturing Medical Vial

ABSTRACT

[Object] To provide a means manufacturing a medical vial which contains a Type IA borosilicate glass as the raw material and in which the elution amount of silica into a high ionic strength solution decreases to be equal to or less than the silica elution amount in a Type IB borosilicate glass. 
     [Solution] A method for manufacturing a medical vial is a method for manufacturing a medical vial including a fire blast process of applying a flame ejected from a point burner to a deteriorated layer generated on the inner surface of a vial, in which the vial is molded from a glass tube containing a Type IA borosilicate glass as the raw material and the molar ratio of oxides contained in the borosilicate glass satisfies ψ=0.23±0.02 in ψ=[(Na 2 O+K 2 O)—Al 2 O 3 ]/B 2 O 3  and satisfies β=7.5±0.5 in β=B 2 O 3 /Al 2 O 3 .

TECHNICAL FIELD

The present invention relates to a method for manufacturing a medicalvial with less elution of silica and the like from a glass wall innersurface.

BACKGROUND ART

As raw materials of a medical glass container, such as a medical vial,borosilicate glass excellent in chemical durability has been used inmany cases. The borosilicate glass is molded into a glass tube to beused as a raw material of the medical glass container. Such a glass tubeincludes Type I, Class B having an expansion coefficient (×10⁻⁷/K) of 48or more and 56 or less (hereinafter also referred to as Type IB) andType I, Class A having an expansion coefficient (×10⁻⁷/K) of 32 or moreand 33 or less (hereinafter also referred to as Type IA) described inNon-Patent Literature 1 (Non-Patent Literature 1). A medical vialmanufactured using glass having a low expansion coefficient as the rawmaterial is hard to cause breakage due to rapid temperature changes.Therefore, a Type IA borosilicate glass tube having a low expansioncoefficient has been used as the raw material of the medical vial whichis required to have durability against rapid temperature changes, suchas freezing/thawing.

In order to manufacture a medical vial from the borosilicate glass tube,a mouth portion and a bottom portion of the vial are molded in the glasstube by heating with high temperature flames. In a process in which thebottom portion is molded from the glass tube, alkaline componentsvolatilized from the glass tube due to the heating of the glass tubecondense particularly on the inner surface near the bottom portion, sothat a deteriorated layer is formed. The alkaline components are elutedfrom such a deteriorated layer into a pharmaceutical agent and the likein the vial. To address the problem, the alkaline component of elutionstandard is established in European Pharmacopoeia and United StatesPharmacopeia and ISO4802-1 or ISO4802-2.

As a method for reducing the elution of alkaline components, an ammoniumsulfate treatment method including causing alkaline components andsulfate present in a deteriorated layer to react with each other togenerate sodium sulfate (Na₂SO₄), and then removing the sodium sulfateby washing with water and a chemical vapor deposition (CVD method)including covering a vial inner surface with a silica (SiO₂) thin filmare known (Patent Literature 1). Moreover, it is known that adeteriorated layer generated on the inner surface of a vial is subjectedto fire blasting with an oxygen-gas flame by a point burner whilerotating the vial molded from a glass tube, whereby the deterioratedlayer is removed, so that the elution of alkaline components is reduced(Patent Literatures 2 and 3).

CITATION LIST Patent Literatures

-   [Patent Literature 1] Japanese Examined Patent Application    Publication No. 6-76233-   [Patent Literature 2] International Publication No. WO2006/123621-   [Patent Literature 3] Japanese Unexamined Patent Application    Publication No. 2010-269973

Non-Patent Literatures

-   [Non Patent Literature 1] ASTM INTERNATIONAL Designation: E 438-92    (Preapproved 2011)-   [Non-Patent Literature 2] “Evaluation of the Inner Surface    Durability of Glass Containers” USP 1660-   [Non-Patent Literature 3] “Delamination Propensity of Pharmaceutical    Glass Containers by Accelerated Testing with Different Extraction    Media”, PDA J Pharm Sci and Tech, 2012, 66116-125

SUMMARY OF INVENTION Technical Problems

In recent years, in addition to the problem of the elution of alkalinecomponents, mixing of silica particle and flakes separated from theinner surface of a vial in a pharmaceutical agent in the vial isregarded as a problem. In the description of <1660>“Evaluation ofdurability of glass container inner surface” in United StatesPharmacopeia (USP), a vial screening method is described which includesevaluating the amount of silica (SiO₂) eluted by heating the vial at121° C. for 2 hours using a high ionic strength solution of 0.9% KClaqueous solution (pH 8.0) (Non-Patent Literature 2).

A vial containing a Type IA borosilicate glass as the raw material isexcellent in water resistance and acid resistance. On the other hand,when an evaluation of the durability against a high ionic strengthsolution using an alkaline 0.9% KCl aqueous solution (pH 8.0) isperformed, the elution amount of silica from the vial is very large ascompared with that of a Type IB borosilicate glass, so that a risk ofthe generation of flakes of silica (SiO₂) is high. Therefore, a negativeconclusion to the use of the Type IA borosilicate glass for a vialstoring an alkaline high ionic strength solution is drawn (Non-PatentLiterature 3).

The present invention has been made in view of the above-describedcircumstances. It is an object of the present invention to provide ameans reducing the elution amount of silica into a high ionic strengthsolution in a medical vial molded using a Type IA borosilicate glasshaving a low expansion coefficient and excellent heat shock resistanceas the raw material to be equal to or less than the silica elutionamount in the case of a medical vial molded using a Type IB borosilicateglass.

Solution to Problems

(1) A method for manufacturing a medical vial according to the presentinvention is a method for manufacturing a medical vial including a fireblast process of applying a flame ejected from a point burner to adeteriorated layer generated on the inner surface of a vial, in whichthe vial is molded from a glass tube containing a Type IA borosilicateglass as the raw material and the molar ratio of oxides contained in theborosilicate glass satisfies ψ=0.23±0.02 in ψ==[(Na₂O+K₂O)—Al₂O₃]/B₂O₃and satisfies β=7.5±0.5 in β=B₂O₃/Al₂O₃.

The medical vial is manufactured by performing heat processing of aglass tube. When the borosilicate glass as a material of the glass tubeis heated, alkali borate contained in the borosilicate glass isvolatilized. When the volatilized alkali borate condenses on the innersurface of the vial, a deteriorated layer is generated. In the fireblast process, the deteriorated layer generated on the inner surface ofthe vial is discharged to the outside.

Moreover, the Type IA borosilicate glass has high durability againsttemperature changes. Therefore, a medical vial obtained using the TypeIA borosilicate glass as the raw material has durability againsttemperature changes.

The structure and the physical properties of the Type IA borosilicateglass vary depending on the content of oxides (Na₂O, K₂O, Al₂O, andB₂O₃) contained in the borosilicate glass. As the molar ratio of theoxides contained in the Type IA borosilicate glass, ψ is approximately ¼in ψ=[(Na₂O+K₂O)—Al₂O₃]/B₂O₃ (M. B. Volf: Technical Approach to Glass.Elsevier, 1990, p. 161). Among the above, the molar ratio of oxidescontained in atypical Type IA borosilicate glass satisfies ψ=0.23±0.02.

When the Type IA borosilicate glass satisfies β=7.5±0.5 in β=B₂O₃/Al₂O₃in addition to the fact that the Type IA borosilicate has thecomposition conditions described above, silica (SiO₂) which is easilyseparated is present in a deteriorated layer of a medical vialmanufactured from the borosilicate glass. The deteriorated layer iseasily removed by the fire blast (FB) process. Therefore, a vial isobtained which has an elution amount of silica into a high ionicstrength solution equal to the silica elution amount in a medical vialprocessed from a Type IB borosilicate glass tube.

(2) Preferably, a value obtained by quantifying silica eluted into ahigh ionic strength solution having a KCl concentration of 0.9 wt/wt %and a pH of 8 from an area per cm² in the total surface area of the vialby heating the vial after the fire blast process at 121° C. for 2 hoursin a state where the vial is immersed in the high ionic strengthsolution using an ICP-AES method is 20.0 μg/cm² or less.

(3) Preferably, the high ionic strength solution is a solutioncontaining 0.1 mol/L or more of alkali salt.

Advantageous Effects of Invention

According to the present invention, in a medical vial molded using aType IA borosilicate glass as the raw material, the elution amount ofsilica into a high ionic strength solution can be reduced to be equal tothe silica elution amount in the case of using a Type IB borosilicateglass.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a view for explaining a fire blast process.

FIG. 2 is a graph showing the relationship between the amount of silica(SiO₂) eluted from a glass tube, a vial before fire blast treatment, anda vial after fire blast treatment and β relating to the composition ofoxides contained in a glass tube as the raw material of each of theglass tube, the vial before fire blast treatment, and the vial afterfire blast treatment.

DESCRIPTION OF EMBODIMENTS

Hereinafter, a preferable embodiment of the present invention isdescribed. It is a matter of course that this embodiment is merely oneembodiment of the present invention and the embodiment can be altered inthe range where the scope of the present invention is not altered.

[Vial 10]

As illustrated in FIG. 1, a vial 10 is a container having a bottomportion 11, a side surface portion 12, and a mouth portion 13 in orderfrom the position serving as the bottom portion in use and has aninternal space 14 thereinside. The vial 10 is closed in the bottomportion 11. The vial 10 opens in an end portion of the mouth portion 13.The inner diameter of the mouth portion 13 is narrower than the innerdiameter of the internal space 14. The vial 10 is molded by performingheat processing of a glass tube 20. The vial 10 is an example of amedical vial. The medical vial is a container capable of storingmedicines, living body samples, such as blood and cell suspension,liquid medicines, and the like in order to keep, for example, the samethereinside. The medical vial includes, for example, an intermediatearticle obtained in the middle of a vial molding process, i.e., anintermediate article in which only a bottom portion is formed and amouth portion is not formed, and those equivalent to a medical vial,such as an ampule.

The main raw material of the glass tube 20 is a Type IA borosilicateglass. Borosilicate glass mainly contains five kinds of oxides of silica(SiO₂), boron oxide (B₂O₃), aluminum oxide (Al₂O₃), sodium oxide (Na₂O),and potassium oxide (K₂O). The structure and the physical properties ofthe borosilicate glass vary depending on the composition ratio of theoxides contained in the borosilicate glass.

In the silica (SiO₂) as the main component, a silicon (Si) atom isbonded to four oxygen (O) atoms to form a network structure in glass. Anoxygen [≡Si—O—Si≡] atom bonded to two Si atoms is referred to ascrosslinking oxygen. On the other hand, Na₂O and K₂O bonded to silicaform non-crosslinking oxygen of [≡Si—O—Na] or [≡Si—O—K]. Thenon-crosslinking oxygen generates a cleavage of the bond in theborosilicate glass. As a result, when the content of Na₂O and K₂O islarge, the expansion coefficient of the borosilicate glass increases andthe chemical durability thereof decreases.

On the other hand, an aluminum ion [AlO₃] bonded to three oxygen (O)atoms in glass attracts non-crosslinking oxygen to form an aluminum ion[AlO₄] bonded to four oxygen (O) atoms to be incorporated into thenetwork structure in glass. As a result, the expansion coefficient ofthe borosilicate glass decreases and the chemical durability thereofincreases.

A boron ion [BO₃] bonded to three oxygen (O) atoms in glass is bonded tonon-crosslinking oxygen remaining after the aluminum ion [AlO₃] isincorporated into the network structure to be incorporated into thenetwork structure. More specifically, in the bond with non-crosslinkingoxygen, an aluminum ion [AlO₃] has priority over a boron ion [BO₃]. Whenan excess amount of aluminum oxide (Al₂O₃) is present and is bonded toall non-crosslinking oxygen atoms, a boron ion is not incorporated intothe network structure and remains to be three-coordinated [BO₃]. As aresult, the chemical durability against a high ionic strength solutionof the borosilicate glass decreases.

As the raw material of the glass tube 20, borosilicate glass ispreferably used in which the molar ratio of the oxides contained in theborosilicate glass satisfies ψ=0.23±0.02, i.e., ψp=0.21 or more and 0.25or less, in ψ=[(Na₂O+K₂O)—Al₂O₃]/B₂O₃. ψ is determined by dividing thenumber of moles of the non-crosslinking oxygen remaining after aluminumion [AlO₃] is incorporated into the network structure by the number ofmoles of B₂O₃ in the borosilicate glass. ψ is a parameter relating tothe composition ratio of Na₂O, K₂O, Al₂O₃, and B₂O₃. Therefore, ψ istreated as a parameter showing the structure and the physical propertiesaffected by the composition of the borosilicate glass. When a glass tube20 of Type IA having ψ of less than 0.21 is used, the elution amount ofsilica into a high ionic strength solution of the obtained vial 10increases. The high ionic strength solution refers to a solutioncontaining 0.1 mol/L or more of alkali salt. Examples of the alkali saltinclude KCl and the like, for example. Examples of the high ionicstrength solution include, for example, a KCl aqueous solution having aconcentration 0.9 wt/wt % (pH 8) and the like. When a glass tube 20 ofType IA having ψ of larger than 0.25 is used, a three-coordinated boronion [BO₃] increases, and the chemical durability of the vial 10 againsta high ionic strength solution decreases.

As the raw material of the glass tube 20, it is preferable to useborosilicate glass satisfying β=7.5±0.5, i.e., β is 7.0 or more and 8.0or less, in β=B₂O₃/Al₂O₃ obtained by dividing the molar ratio of B₂O₃ bythe molar ratio of Al₂O₃ in addition to the molar ratio conditionsdescribed above. The durability against a high ionic strength solutionof the borosilicate glass having such a β value is high as in the caseof a Type IB borosilicate glass. A deteriorated layer generated in amedical vial manufactured from the borosilicate glass is easily removedby the fire blast process. The deteriorated layer is one in which alkaliborate volatilized from borosilicate glass heated to a high temperatureis denatured by reacting with the borosilicate glass. The deterioratedlayer is the cause of the elution of alkaline components into a solutionand the generation of silica particle and flakes.

In the case where an excess amount of boron oxide in the borosilicateglass is present relative to aluminum oxide, the elution amount ofsilica into the high ionic strength solution from the deteriorated layerincreases when β is larger than 8.0, for example. When β is smaller than7.0, the viscosity of the borosilicate glass increases, which makes itdifficult to melt the glass.

[Method for Manufacturing Vial 10]

A method for manufacturing the vial 10 includes a vial molding processand a fire blast process. The vial molding process is a process ofprocessing and molding the shape of the vial 10 from the glass tube 20.The fire blast process is a process of applying a flame 31 ejected froma point burner 30 to an inner surface 15 of the vial 10.

In the vial molding process, alkali borate, such as NaBO₂ and/or HBO₂,is volatilized by heating from the borosilicate glass forming the glasstube 20. The volatilized alkali borate condenses near the bottom portion11 on the inner surface 15 of the molded vial 10. The condensed alkaliborate reacts with the borosilicate glass near the bottom portion 11, sothat a deteriorated layer is generated near the bottom portion 11. Inthe deteriorated layer, silica is likely to be eluted into a high ionicstrength solution or separated. The high ionic strength solution refersto a solution containing 0.1 mol/L or more of alkali salt. Examples ofthe high ionic strength solution include a 0.9 wt/wt % (pH 8) KClaqueous solution, for example.

After the vial molding process, the inside of the vial 10 was filledwith a 0.05 wt/wt % methylene blue solution, and then the vial 10 isallowed to stand still for 20 minutes. Subsequently, the methylene bluesolution is discharged from the inside of the vial 10, and then the vial10 is washed with distilled water. The washed vial 10 is heated at 120°C. for 10 minutes to be dried. The methylene blue is adsorbed to adeteriorated layer, and thus the deteriorated layer on the vial innersurface is colored with the methylene blue. This clarifies a portionwhere the deteriorated layer to be removed is present. The deterioratedlayer is likely to be generated near the bottom portion 11.

[Fire Blast Process]

In order to remove the deteriorated layer generated on the inner surface15 of the molded vial 10, a fire blast process is performed. The fireblast process is a process of applying a flame ejected from the pointburner 30 to the inner surface 15 of the vial 10. During the fire blastprocess, the vial 10 is rotated. As illustrated in FIG. 1, the pointburner 30 has a burner body 33 and a nozzle 32 and is connected to aflow rate control device (not illustrated) of inflammable gas andoxygen. A known device can be used as the flow rate control device. Thenozzle 32 is connected to the tip side of the burner body 33. The nozzle32 has a straw shape and allows a mixed gas flowing out of the burnerbody 33 to pass therethrough. The outer diameter of the nozzle 32 allowsthe insertion of the nozzle 32 into an internal space 14 of the vial 10and is sufficiently smaller than the inner diameter of a neck portion 18of the vial 10. The length in the axial direction of the nozzle 32 issufficiently larger than the length along the axial direction of thevial 10. As a raw material of the nozzle 32, one having high heatresistance, such as ceramic, is preferable, for example.

The nozzle 32 at the tip of the point burner 30 is inserted into theinternal space 14 of the vial 10 through the mouth portion 13. The gasand the oxygen drawn into the point burner 30 are mixed. The gas isinflammable gas, and methane gas is mentioned, for example. The mixedgas is ejected from the nozzle 32. The mixed gas is ejected as the flame31 while burning. The flame 31 ejected from the nozzle 32 is sprayedonto the inner surface 15 of the vial 10. The spraying of the flame 31is performed for about 10 seconds, when the capacity of the vial is 5mL, for example. Moreover, the spraying of the flame 31 is preferablyperformed so that the flame 31 is applied to the vicinity of the bottomportion 11 where the deteriorated layer is present.

The tip of the nozzle 32 is adjusted so that the distance between thetip of the nozzle 32 and the inner surface of the vial has a fixeddistance in such a manner that the most optimal portion of the flame 31ejected from the nozzle 32 is applied to the inner surface 15 of thevial 10. The most suitable portion of the flame 31 is a portioncontaining the largest amount of plasma. The portion rich in plasma ofthe flame 31 is a portion rich in oxonium ion (H₃O⁺) (POSITIVE ION PROBEOF METHANE-OXYGEN COMBUTION, J. M. GOODINGS and D. K. BOHME,International Symposium on Combustion, Volume 16, Issue 1, 1977, Pages891-902).

The plasma contained in the flame 31 evaporates and removes thedeteriorated layer generated on the inner surface 15 of the vial 10.Substances forming the removed deteriorated layer are discharged to theoutside from the vial 10.

The rotation of the vial 10 is performed by the rotation of the supportbase 34 supporting the vial 10, for example. The support base 34 may bemoved up and down so that the flame 31 is uniformly applied in thevertical direction of from the mouth portion 13 to the bottom portion 11of the vial 10. Thus, the flame 31 is applied to the entire innersurface 15 of the vial 10 while being scanned, so that the deterioratedlayer generated on the inner surface 15 of the vial 10 is sufficientlyremoved.

The position where the deteriorated layer is present in the vial 10varies depending on a method for molding the vial 10, e.g., a methodincluding molding the vial 10 with the axis line of the glass tube 20along the vertical direction, a method including molding the vial 10with the axis line of the glass tube 20 along the horizontal direction,the fact that either the bottom portion 11 or the mouth portion 13 ofvial 10 is formed first, and the like. Therefore, when the deterioratedlayer widely spreads on the inner surface 15 of the vial 10, forexample, the support base 34 may be moved so that the flame 31 isuniformly applied to the entire inner surface 15 of the vial 10.

[Operational Effects of this Embodiment]

According to this embodiment, in the vial 10 molded using the Type IAborosilicate glass to be used for storing pharmaceutical agents and thelike as the raw material, the vial 10 is obtained from which thedeteriorated layer generated on the inner surface 15 of the vial 10 isremoved. Therefore, the amount of silica (SiO₂) eluted from the vial 10into a high ionic strength solution decreases. Therefore, bypassingthrough the fire blast process, the vial 10 molded using the Type IAborosilicate glass as the raw material has not only high durabilityagainst rapid temperature changes in freeze dry but excellent durabilityagainst a high ionic strength solution equivalent to the durability of avial molded using a Type IB borosilicate glass as the raw material.

[Modification]

The embodiment described above describes the method for manufacturingthe vial 10 as a medical glass container. However, manufacturing ofampules, syringes, medicine bottles, and the like as a medical glasscontainer can also be achieved.

EXAMPLES

Hereinafter, Examples of the present invention are described.

Examples 1 and 2

In Examples 1 and 2, glass tubes 20 molded from a Type IA borosilicateglass were used. The compositions (mol %) of the borosilicate glass ofthe glass tubes 20 used for Examples are shown in Table 1.

TABLE 1 Type IA glass composition (mol %), ψ, β, and silica (SiO₂)elution amount (μg/cm²) due to heating at 121° C. for 2 hours when asolvent is distilled water for injection Composition (mol %) ASTM ASTMType Com. Type IA Ex. Ex. 1 Ex. 2 IB SiO₂ 83.27 82.16 83.04 83.12 B₂O₃11.53 12.29 11.51 11.15 Al₂O₃ 1.21 1.34 1.47 1.55 Na₂O 3.99 4.20 3.624.15 K₂O 0.00 0.00 0.36 0.03 ψ 0.241 0.233 0.218 0.236 β 9.53 9.17 7.837.19 SiO₂ Glass 0.2 0.2 0.2 0.4 elution tube amount Standard 3.8 2.8 2.313.8 (μg/cm²) vial FB vial 0.1 0.1 0.1

As shown in Table 1, the molar ratio of the oxides contained in theborosilicate glass in the glass tubes 20 used for Examples 1 and 2satisfied ψ=0.23±0.02 in ψ=[(Na₂O₊K₂O)—Al₂O₃]/B₂O₃ and satisfiedβ=7.5±0.5 in β=B₂O₃/Al₂O₃. Na₂O, K₂O, Al₂O₃, and B₂O₃ in the equationsrepresent the molar ratio (mol %) of each oxide contained in theborosilicate glass.

[Manufacturing of Vial 10]

In a vial molding process, a vial having a capacity of 3 mL was createdfrom the glass tube 20. Moreover, the processing of the vial 10 wasperformed using a standard vertical die molding machine. After the vialmolding process, the inside of the vial 10 was filled with a 0.05 wt/wt% methylene blue solution, and then the vial 10 was allowed to standstill for 20 minutes. Subsequently, the methylene blue solution wasdischarged from the inside of the vial 10, and then the inside of thevial 10 was washed with distilled water. The washed vial 10 was dried at120° C. for 10 minutes. Thus, the deteriorated layer on the vial innersurface was colored with the methylene blue, so that a region where thedeteriorated layer was present was able to be visually observed.

The created vial 10 was subjected to the fire blast process in theembodiment described above. As the nozzle of the point burner 30, analumina nozzle having an inner diameter of 1.0 mm was used. As fuel, amixed gas was used in which methane gas and oxygen were mixed. As themixed gas, a mixed gas was used in which methane gas with a flow rate of0.5 L/min and oxygen with a flow rate of 1.1 L/min were mixed. A flameejected from the nozzle of the point burner 30 was applied to the regionwhere the deteriorated layer was present of the inner surface 15 of thevial 10. The vial 10 was rotated with a rotating machine or the like. Bythe rotation of the vial 10, the flame was uniformly applied to theentire inner surface 15 of the vial 10. Thus, vials 10 of Examples 1 and2 were obtained.

Comparative Example

In Comparative Example, a glass tube 20 molded from a Type IAborosilicate glass was used. In Comparative Example, the glass tube 20was used in which the molar ratio of the oxides contained in theborosilicate glass satisfied ψ=0.23±0.02 in ψ=[(Na₂O+K₂O)—Al₂O₃]/B₂O₃but did not satisfy β=7.5±0.5 in β=B₂O₃/Al₂O₃. The composition of theborosilicate glass in the glass tube 20 used for Comparative Example isshown in Table 1.

A vial 10 of Comparative Example was molded by the same vial moldingprocess as that of Examples. The fire blast process in the vial 10 ofComparative Example was also performed in the same manner as inExamples.

[Elution Amount of Silica (SiO₂) from Glass Tube 20]

The silica elution amount was measured for each glass tube 20 used forExamples 1 and 2 and Comparative Example. As a solvent for elution,distilled water for injection or a KCl aqueous solution having aconcentration of 0.9 wt/wt % (pH 8) was used. The KCl aqueous solutionis an aqueous solution in which the pH was adjusted to 8 by adding aNaOH aqueous solution so that the KCl concentration finally reached 0.9wt/wt %. The distilled water for injection or the KCl aqueous solutionhaving a concentration of 0.9 wt/wt % (pH 8) as the solvent was chargedinto a Teflon (Registered Trademark) beaker. Each glass tube wasimmersed in the Teflon (Registered Trademark) beaker charged with thesolvent. Each immersed glass tube 20 was heated at 121° C. for 2 hoursusing an autoclave with Teflon (Registered Trademark) beaker. Aftercooling, the amount of the silica eluted into the solvent in each Teflon(Registered Trademark) beaker was measured. The measurement of thesilica was performed by an ICP-AES method (Inductively Coupled PlasmaAtomic Emission Spectrometry). The amount (μg/cm²) of the silicaobtained for each glass tube 20 of Examples 1 and 2 and ComparativeExample is shown in Tables 1 and 2. Table 1 shows the silica elutionamount when distilled water for injection was used as the solvent forelution. Table 2 shows the silica elution amount when the KCl aqueoussolution having a concentration of 0.9 wt/wt % (pH 8) was used as thesolvent for elution. The amount (μg/cm²) of the eluted silica wasexpressed as a value per cm² of the surface area of each glass tube 20.The surface area of the glass tube 20 was determined by calculation fromthe inner diameter of the standard, the outer diameter of the standard,and the actual length in terms.

TABLE 2 ψ and β of Type IA glass and silica (SiO₂) elution amount(μg/cm²) due to heating at 121° C. for 2 hours when a solvent is 0.9%KCl (pH 8) Composition (mol %) ASTM ASTM Type Com. Type IA Ex. Ex. 1 Ex.2 IB ψ 0.241 0.233 0.218 0.236 β 9.53  9.17 7.83 7.19 SiO₂ Glass 23.310.5 6.4 4.1 elution tube amount Standard 51.2 26.9 13.4 11.3 (μg/cm²)vial FB vial 50.0 17.6 7.3

As shown in Table 1, when the solvent was distilled water for injection,the elution amounts of the silica from the glass tubes 20 of Examples 1and 2 and Comparative Example were all 0.2 μg/cm² and were equal inExamples and Comparative Example. Therefore, it was confirmed that theType IA borosilicate glass satisfying ψ=0.23±0.02 was excellent in waterresistance.

On the other hand, as shown in Table 2, when the solvent was the KClaqueous solution having a concentration of 0.9 wt/wt % (pH 8), theelution amounts of the silica from the glass tubes 20 of Examples 1 and2 and Comparative Example decreased with the reduction of the β values.As compared with Comparative Example having a β value of 9.17, numericalvalues close to the value of the glass tube 20 containing the Type IBborosilicate glass as the raw material were obtained as the silicaelution amounts of Examples 1 and 2.

The glass tube 20 molded from a Type IB borosilicate glass having anexpansion coefficient of (×10⁻⁷/K) 51 was examined for the elution ofsilica in the same manner as in Examples. In the glass tube 20 moldedfrom the Type IB borosilicate glass, the silica elution amount was 4.1(μg/cm²).

[Elution Amount of Silica (SiO₂) from Vial 10]

The silica elution amount was measured for each vial 10 of Examples 1and 2 and Comparative Example described above. In the vials 10 obtainedin Examples 1 and 2 and Comparative Example described above, the silicaelution amount was measured by the same method as that of themeasurement of the elution amount of silica from the glass tube 20,except charging the solvent to 90% of the full capacity of the vial as asilica elution process. The amounts (μg/cm²) of the silica obtained foreach vial 10 of Examples 1 and 2 and Comparative Example are shown inTables 1 and 2. Table 1 shows the silica elution amount when distilledwater for injection was used as the solvent for the elution. Table 2shows the silica elution amount when the KCl aqueous solution having aconcentration of 0.9 wt/wt % (pH 8) was used as the solvent for theelution. The eluted silica amount (μg/cm²) was expressed as a value persurface area of each vial 10. The surface area of the vial 10 wascalculated by CAD from the inner diameter, the outer diameter, thelength, and the like in terms of the standard.

As shown in Table 1, when the solvent was distilled water for injection,the elution amounts of the silica from the vials 10 after the fire blasttreatment of Examples 1 and 2 and Comparative Example were all 0.1μg/cm² and were equal in Examples and Comparative Example. Therefore, itwas confirmed that the vials 10 molded from the glass tube 20 containingthe Type IA borosilicate glass satisfying ψ=0.23±0.02 were alsoexcellent in water resistance.

As shown in Table 2, when the solvent was the KCl aqueous solutionhaving a concentration of 0.9 wt/wt % (pH 8), it was confirmed that 17.6μg/cm² of silica and 7.3 μg/cm² of silica were eluted from the vial 10after the fire blast treatment of Example 1 and from the vial 10 afterthe fire blast treatment of Example 2, respectively. On the other hand,it was confirmed that 50.0 μg/cm² of silica was eluted from the vial 10after the fire blast treatment of Comparative Example. It was confirmedfrom the results that, in the vial 10 molded from the glass tube 20containing the Type IA borosilicate glass satisfying β=7.5±0.5, thesilica elution amount was reduced to half or less of the silica elutionamount in the case where 13=7.5±0.5 was not satisfied and the elutionamount was 20.0 μg/cm² or less. The numerical values of the silicaelution amounts of the vials 10 of Examples 1 and 2 after the fire blasttreatment were equal to or less than the value (11.3 μg/cm²) of the vial10 molded from the glass tube 20 containing the Type IB borosilicateglass as the raw material.

FIG. 2 is a graph showing the relationship between β relating to thecomposition of the borosilicate glass and the amount of silica (SiO₂)eluted due to heating at 121° C. for 2 hours using the high ionicstrength solution of 0.9 wt/wt % KCl aqueous solution (pH 8). In FIG. 2,A (♦) represents the results of the glass tubes 20 as the raw materialof Examples 1 and 2 and Comparative Example, B (•) represents theresults of the vials 10 before the fire blast treatment of Examples 1and 2 and Comparative Example, and C (◯) represents the results of thevials 10 after the fire blast treatment of Examples 1 and 2 andComparative Example. In FIG. 2, the Y-axis represents the amount of thesilica (SiO₂) eluted due to heating at 121° C. for 2 hours using a highionic strength solution of 0.9 wt/wt % KCl aqueous solution (pH 8) andthe X-axis represents the β values.

For comparison, a glass tube 20 containing a Type IB borosilicate glassas the raw material and a standard vial 10 molded from the glass tube 20containing a Type IB borosilicate glass as the raw material wereconfirmed for the elution of the silica into the 0.9 wt/wt % KCl aqueoussolution (pH 8) in the same manner as in Examples. The standard vial isa vial which was not subjected to surface treatment, such as ammoniumsulfate treatment and fire blast treatment. In FIG. 2, a straight line Drepresents the elution amount of the silica from the glass tube 20containing the Type IB borosilicate glass as the raw material and astraight line E represents the elution amount of the silica from thestandard vial 10 molded from the glass tube 20 containing the Type IBborosilicate glass as the raw material.

From the eluted silica amount and the 1 values, each approximationstraight line illustrated in FIG. 2 were obtained by a least-squaremethod. It was accepted that, in the Type IA borosilicate glass, theelution of the silica from the glass tube into the high ionic strengthsolution is further reduced with a reduction in the t values. The amountof the silica eluted from the glass tube of the Type IA approaches theamount of the silica eluted from the glass tube of Type IB in the rangeof β=7.5±0.5. More specifically, it was confirmed for the vial 10 moldedfrom the glass tube 20 containing the Type IA borosilicate glass as theraw material that the elution of the silica into to the high ionicstrength solution was equal to or less than the value of the vial 10molded from the glass tube 20 containing the Type IB borosilicate glassas the raw material in the range of β=7.5±0.5.

REFERENCE SIGNS LIST

-   10 Vial-   15 Inner surface-   20 Glass tube-   30 Point burner-   31 Flame

1. A method for manufacturing a medical vial comprising: a fire blaststep of applying a flame ejected from a point burner to a deterioratedlayer generated on an inner surface of a medical vial, wherein the vialis molded from a glass tube containing a Type IA borosilicate glass as araw material; and a molar ratio of oxides contained in the borosilicateglass satisfies ψ=0.23±0.02 in ψ=[(Na₂O+K₂O)—Al₂O₃]/B₂O₃ and satisfiesβ=7.5±0.5 in β=B₂O₃/Al₂O₃.
 2. The method for manufacturing a medicalvial according to claim 1, wherein a value obtained by quantifyingsilica eluted into a high ionic strength solution having a KClconcentration of 0.9 wt/wt % and a pH of 8 from an area per cm² in atotal surface area of the vial by heating the vial after the fire blaststep at 121° C. for 2 hours in a state where the vial is immersed in thehigh ionic strength solution using an ICP-AES method is 20.0 μg/cm² orless.
 3. The method for manufacturing a medical vial according to claim2, wherein the high ionic strength solution is a solution containing 0.1mol/L or more of alkali salt.